OBITUARIES : Dr. Thomas H. Weller, 1915 - 2008

Nobelist's work key in fight against polio

Dr. Thomas H. Weller, the Harvard virologist who shared the 1954 Nobel Prize in medicine for developing techniques to grow the polio virus in the laboratory, a feat that laid the groundwork for the development of the polio vaccine and the feared virus' near-eradication from the world, died in his sleep Saturday at his home in Needham, Mass. He was 93.

The techniques developed by Weller, Dr. John F. Enders and Dr. Frederick C. Robbins made it possible to grow a host of other viruses in the laboratory and led to the creation of many other vaccines.

Weller also isolated the rubella (German measles) and herpes zoster viruses and demonstrated that the rubella virus and cytomegalovirus could be transmitted congenitally to fetuses, producing birth defects.

Weller "was one of the great scientists of the 20th century and a leader in neglected tropical diseases," said Dr. Dyann Wirth, chairwoman of the department of immunology and infectious diseases at the Harvard School of Public Health, where Weller spent most of his career. "He inspired many during his lifetime, and his vision led an entire field for many decades. His legacy is one to be remembered."

For The Record Los Angeles Times Saturday, August 30, 2008 Home Edition Main News Part A Page 2 National Desk 1 inches; 45 words Type of Material: Correction Weller obituary: The obituary of Nobel laureate Dr. Thomas H. Weller in Wednesday's California section said Weller had isolated the herpes zoster virus and demonstrated that it was identical to the rubella virus. Weller found that the herpes zoster and varicella viruses are the same.

In the late 1940s, when Weller and Robbins were research fellows in Enders' Harvard laboratory, viruses could not be seen with the tools then available. Working with the viruses required injecting them into monkeys or other laboratory animals and observing their effects.

Small amounts of the polio virus had been isolated from the brain and nervous system of monkeys, but attempts to produce a vaccine from them were failures or even catastrophic. Some of the vaccines simply did not work, while others were contaminated with nerve tissue that produced disastrous inflammation in the brains of recipients.

The Harvard trio stumbled upon their discovery almost by accident. It was, Weller later wrote, "almost an afterthought." They had been trying to grow the varicella (chickenpox) virus in a mixture of human embryonic nerve, skin, muscle and gut cells.

"We had no immediate intention of carrying out experiments with poliomyelitis viruses," they wrote in their 1949 paper in the journal Science describing the research. "Nevertheless, from time to time, we had considered the mounting evidence" that the polio virus might be able to grow in tissues other than nerve cells.

With the varicella experiments going nowhere, the team decided to lace some of its culture media with a polio strain stored in the laboratory refrigerator. To their great surprise, the virus proliferated readily. Furthermore, the virus altered the appearance of cells it infected, making it easy to track the progress of the infection.

Their findings sparked further research, which showed that the polio virus enters the body through the mouth, multiplies in the intestines and occasionally passes into the bloodstream. The virus enters the brain in about 1 out of every 200 people infected and causes paralysis and other severe symptoms of the disease.

With large amounts of the virus available -- Weller noted that one test tube of the virus was equal to one monkey's worth -- other researchers quickly began working on vaccines. In 1954, Dr. Jonas Salk began national testing of the killed-virus vaccine that was administered by an injection. Eight years later, Dr. Albert Sabin introduced a live-virus vaccine that could be absorbed into a sugar cube and given orally.

With the introduction of the vaccines, the number of U.S. paralytic polio cases fell from 16,000 in 1949 to a handful in 1970. The disease has now been nearly eradicated from the world, with only small pockets of infection in certain African countries where the Western vaccine is viewed with great suspicion.

In 1960, Weller had been trying without success to isolate the rubella virus when his then-10-year-old son, Robert, developed an unusually severe case of the disease. Weller infused Robert's urine into cultures of human amnion tissue -- the membrane surrounding the fetus.

Nothing much happened initially. But Weller maintained the cultures much longer than was thought to be necessary. On the 26th day, he saw changes in the cells and was finally able to culture the virus. With Dr. Franklin Neva of Harvard, he collected specimens from other rubella outbreaks and showed that they contained the same virus.

At the same time, the pair discovered that a team at the Walter Reed Army Institute of Research in Washington had isolated a rubella virus. With the help of Sabin and others, the two teams exchanged viruses and showed that they were the same. Their papers were published back-to-back in the October 1962 issue of the Proceedings of the Society of Experimental Biology and Medicine.

Weller also isolated the herpes zoster virus, which causes shingles, and demonstrated that it was identical to the rubella virus.

He and his colleagues were also ultimately successful in isolating the chickenpox virus.